Small animals such as rodents are used extensively in clinical research. Some rodents, particularly certain mice and rats, are acceptable genetic analogues to humans and are subjects for tests of drug and genetic therapies as well as other tests. To this end there is a critical need to image the back of the eye. This imaging is needed both to test therapies for eye diseases and to detect the ocular side effects of drugs administered for other diseases. In this later instance it is possible to add a fluorescent tag to the drug to detect its presence in the eye.
The mouse eye is typically about 3 millimeters in diameter and the rat eye is typically about 6 millimeters in diameter, this compared to the average human eye at about 25 millimeters in diameter. As a result of the tiny size of the rodent eye, the use of standard human eye imaging systems for rodents is difficult or impossible. Even when conventional cameras produce images, they are limited in resolution, field of view, and are very difficult to use.
There is a substantial need for wide-field and high resolution imaging of the rodent eye (which can be in color) with the option for fluorescent angiography and fluorescent imaging (auto-fluorescence) and with means suitable for every day use in a production environment because many studies involve large numbers of animals.
In FIG. 2 is shown at the same scale the eye of the human 8 and an eye 39 of a mouse. The rat eye has the same general features as the mouse eye but is about 6 millimeters in diameter. Besides the substantial difference in size the eyes of the human and rodent differ in other significant features and in FIG. 3 the eye 39 of a mouse is shown at an expanded scale to show details. First, most of the refractive power of the human eye is in the protruding cornea 10 whereas in the rodent eye, which is nearly spherical, the large crystalline 11 lens provides most of the refractive power. Second, the human eye is recessed so that the bones about the eye can protect the eye from mechanical injury whereas the rodent eye protrudes from the head. Third, the eyes of the rodent are located more on the side of the head rather than frontally as in the human. Fourth, the human eye can only dilate so that at best the optical system is f/3 whereas the rodent can dilate to nearly f/1.3.
There is currently no known imaging system specifically designed for imaging the back of the rodent eye. Cameras designed for use with human subjects usually image at a stand off distance of 10 cm. These cameras require a cooperative subject who will place their head in a chin/forehead rest. And, the minimum pupil diameter requirement for the so-called “non-mydriatic” cameras is 4 millimeters. The largest dilation with the larger rat eye is 4 millimeters and with the mouse 2 millimeters but the curvature of the back of the rat eye has a diameter of 6 millimeters whereas that of the human eye has a curvature of 25 millimeters diameter. Accordingly, only a small portion of an image of an eye 39 of a mouse or rat will be in focus. Indeed images of the rat eye are obtained but with great difficulty in university settings and the images are of very poor quality. Similar results and limitations apply to the use of the scanning laser ophthalmoscope (SLO) to this problem and the SLO does not provide for color imaging.
Although the invention is not limited to the following features and advantages, some embodiments of the invention can provide the following: wide-field, high resolution imaging of the back of the rodent eye with the option of providing fluorescent angiography and fluorescent imaging (auto-fluorescence); versatility to image mice, rats, and larger animals such as rabbits and monkeys; and images at fields of view (FOV) of at least 60 degrees and with resolutions below 5 microns.